Summary of Haemostasis, Blood Coagulation Process and Antithrombotic Drugs

• Haemostasis is a vital process that prevents excessive bleeding through platelet activation and fibrin formation, crucial for maintaining vascular integrity.
• Thrombosis, characterized by abnormal clot formation within blood vessels, poses significant health risks and is influenced by Virchow’s triad: endothelial damage, altered blood flow, and increased coagulability.
• Arterial thrombi primarily consist of platelets and fibrin, while venous thrombi include a mix of fibrin and trapped blood cells, with both capable of causing severe complications like embolism.
• Drug therapies targeting haemostasis and thrombosis management focus on altering blood coagulation, modifying platelet function, or enhancing fibrinolysis.
• The coagulation cascade, involving enzymatic activation of clotting factors and feedback loops, culminates in fibrin formation catalyzed by thrombin, regulated by antithrombin III and endothelial mechanisms.
• Understanding these processes and their pharmacological interventions is critical for effectively managing bleeding disorders and preventing thrombotic events.

• Thrombosis Types and Risks:
  • Arterial and venous thrombi are significant causes of morbidity and mortality.
  • Risk factors include age, local trauma, vascular stasis, systemic blood coagulation changes, and genetic/environmental factors.
• Mechanisms of Thrombosis:
  • Arterial thrombosis: Often related to ruptured atherosclerotic plaques, high blood pressure, and turbulent blood flow.
  • Venous thrombosis: Typically occurs in areas of diminished blood flow or stasis; influenced by inherited conditions, immobility, surgeries, cancers, pregnancy, and hormone therapy.
• Classes of Antithrombotic Drugs:
  • Anticoagulants: Inhibit fibrin formation, prevent clot growth, and reduce thromboembolic event risks.
  • Antiplatelet Drugs: Prevent platelet aggregation, reducing the risk of arterial thrombi.
  • Thrombolytics/Fibrinolytics: Dissolve existing clots by breaking down fibrin.
• Anticoagulant Drugs:
  • Heparin and LMWHs: Inactivate factor Xa and, in the case of unfractionated heparin, also thrombin.
  • Vitamin K Antagonists (Warfarin): Inhibit vitamin K-dependent clotting factors, requiring frequent monitoring.
  • Direct Thrombin Inhibitors (Dabigatran): Inhibit thrombin directly, with rapid onset and specific antidotes.
  • Factor Xa Inhibitors (Rivaroxaban, Apixaban): Directly inhibit factor Xa, preventing thrombin formation, with antidotes available for bleeding management.
• Pharmacokinetics and Administration:
  • Anticoagulants vary in onset, administration route, and monitoring needs, with DOACs offering convenience over traditional warfarin.
• Adverse Effects:
  • Common across anticoagulants include bleeding, with varying risks depending on drug class and patient factors.
  • Warfarin has a narrow therapeutic window and multiple drug interactions, requiring careful monitoring.
• Clinical Indications:
  • Antithrombotic drugs are used in preventing and treating venous thromboembolism, managing atrial fibrillation, and during surgeries to prevent clot formation.

• Role of Platelets: Platelets are essential for haemostasis, vascular repair, and inflammation, but their activation can lead to thrombosis in diseased arteries.
• Antiplatelet Drugs: Antiplatelet drugs, including aspirin, P2Y12 inhibitors, and glycoprotein IIb/IIIa receptor inhibitors, are crucial in treating and preventing arterial thrombosis.
• Aspirin: Aspirin inhibits COX-1, reducing platelet aggregation and vasoconstriction, and is a cornerstone in the prevention and treatment of cardiovascular diseases.
• P2Y12 Inhibitors: These drugs block ADP-induced platelet aggregation and are used in acute coronary syndromes and stent implantation. They vary in potency, duration of action, and adverse effects.
• Glycoprotein IIb/IIIa Inhibitors: These parenteral drugs inhibit the final step of platelet aggregation and are used to prevent ischemic complications in coronary procedures.
• Clinical Uses: Antiplatelet drugs are used to manage conditions like myocardial infarction, stroke, and unstable coronary syndromes, often in combination with other antithrombotic therapies.
• Thrombolytic Drugs: These drugs promote fibrinolysis to dissolve clots in acute myocardial infarction and stroke but carry significant bleeding risks and are contraindicated in several conditions.
• Adverse Effects and Contraindications: All antiplatelet and thrombolytic drugs have potential adverse effects, particularly bleeding, and should be used with caution in patients with contraindications such as active bleeding or recent trauma.